The polychlorinated biphenyls (PCBs) are found universally as toxic environmental pollutants. The objectives of the proposed research program are to determine the mechanisms of hepatic microsomal metabolism of selected individual PCBs and to relate this metabolism to the toxicity of the corresponding PCB. The previously developed in vitro microsomal system for the metabolism of PCBs will be utilized to investigate a series of dichloro- and trichlorobiphenyls. Microsomes from control rats and from PCB induced rats will be used in investigations of PCB metabolism. The inducing PCBs will be chosen on the basis of their ability to markedly induce cytochrome P-450 or cytochrome P-448. The role of the number and position of the chlorine substituents on the PCBs in controlling metabolite patterns will be determined and used to predict the metabolic pathways of all forms of PCBs. The effects of PCB induction of microsomal enzymes on subsequent PCB metabolism will be used to predict the role of individual PCBs in the general metabolism of PCB mixtures. Unstable intermediates which have been observed in the metabolism of certain dichlorobiphenyls will be investigated with a view to determining the mechanisms of PCB metabolism and determining the potential of PCB metabolism to produce mutagens.